The dual impacts of the HIV/AIDS pandemic and unintended pregnancies constitute a major health burden for women worldwide. As a consequence, dual protection technologies (DPT) combining safe, effective, and easily reversible options for contraception with a topical microbicide against sexual HIV-1 transmission are a global health priority. However, there is currently no clinically approved female-controlled dual protection technology to prevent sexual HIV-1 transmission and unintended pregnancies. A bottleneck for developing effective DPTs against HIV and unintended pregnancies is in the integration of multiple design criteria into a single device. We hypothesize that patterned electrospun nanofibers impregnated with agents that have specific action against HIV and sperm, and are designed to protect both the cervix and vagina, will provide a chemical and physical barrier for dual-prevention of sexual HIV transmission and pregnancy. We propose a paradigm shift from the development of existing DPTs by using biodegradable nanofibers for vaginal drug delivery that achieve the following specific aims: (1) Electrospin nanofibers for concomitant and sustained release of different chemical classes of agents (small molecule drug and biologics); (2) Fabricate three-dimensional electrospun nanofibers with controlled architecture, mechanical strength, and mucoadhesive properties; (3) measure effect of genital secretions and erosion on the release kinetics and activity of the nanofiber contraceptive microbicide; (4) measure biodistribution and anti-HIV activity of nanofibers in tissue explants; and (5) measure biodistribution and contraceptive activity of nanofibers in a mouse model. The success of this proposal is through integrating research on biomaterials synthesis and characterization, HIV microbicide development and efficacy testing, and non-hormonal contraceptive development and efficacy testing. This novel vaginal drug delivery platform could potentially be used for prevention of other sexually-transmitted or reproductive tract infections alone and in combination, intravaginal delivery of nanoparticles, or be designed for rectal drug delivery.